Obesity is prevalent, is associated with many health hazards, and its treatment replete with frustration. The contribution of alterations in metabolic rate to the development of obesity or its recurrence are controversial. Also, while it is well known that the prevalence of obesity is increased in black American women, there is little known about whether alterations in the metabolic rate may predispose this population to obesity. The current study will use the doubly-labeled water technique to measure ambulatory, free-living metabolic rate in obese caucasian and black American subjects before and after weight reduction to ideal body weight and compare the reduced obese subjects to normal lean controls. In addition, we will follow the reduced obese subjects prospectively to determine if weight gain is related to metabolic rate. Our goal is to determine if reduced obese subjects are at a metabolic disadvantage which will lead to weight gain at 'normal" caloric intake. In addition to these studies, we will also evaluate multiple insulin responsive parameters in vivo in black and caucasian women before and after weight loss and stabilization at ideal body weight and compare these to normal lean populations. We will evaluate insulin resistance with regard to protein metabolism, glucose metabolism and antilipolysis to determine if there is selective insulin resistance in obesity and whether all insulin resistant parameters revert to normal when ideal body weight is achieved. These studies are important since one could postulate that differential insulin resistance (or sensitivity) may be at least partially responsible for the development of obesity. In this regard, we will also evaluate lipoprotein lipase activity, mass, and mRNA levels in black and caucasian subjects before and after weight loss to compare to a normal lean population. We are also developing a functional lipoprotein lipase assay by having patients ingest nonadecanoic acid. This will allow us to determine not only in vitro measures of LPL, but also whether changes in the in vitro activity of LPL express themselves in increased fat uptake in adipose tissue. All of these studies will be performed in caucasian and black populations. The long-term goals of these studies are to help us to understand the etiology of obesity and, thereby, allow us to design more rational therapeutic regimens to enhance our long-term success at treating this important metabolic problem.